BACKGROUND Clinical studies have shown that fluctuation in the plasma concentrations of estrogen during the menstrual cycle has an effect on myocardial health in premenopausal women. When estrogen levels are low, the number of ischemic events experienced is increased. OBJECTIVE To determine whether the increased ischemic events reported with low plasma estrogen concentrations in women could be reproduced in an animal model, cardiac function was measured during hypoxia in the female rat at different time points of the estrous cycle. METHODS Hearts from female Sprague-Dawley rats were perfused in the working mode at the diestrous (low estrogen; n = 7) and proestrous (high estrogen; n = 6) phases of the estrous cycle, confirmed by plasma estradiol concentrations. Hearts were perfused under aerobic conditions with 5.5 mM glucose, 100 muU/mL insulin, and 1.2 mM palmitate, followed by a 30-minute period of hypoxia with 95% N(2)-5% CO(2) gassing. RESULTS There were no significant differences in heart function between diestrous and proestrous groups prior to hypoxia. However, hypoxia induced perturbations in function that were dependent on the estrous cycle. Reductions in left ventricular systolic and diastolic pressure occurred with hypoxia, but no significant differences in these pressures were observed between groups. Left ventricular pulse pressure and coronary flow also decreased significantly during hypoxia (both, P < 0.05), but hearts from the proestrous group maintained a significantly higher pulse pressure (P < 0.05). Hearts from the proestrous group also maintained significantly higher rates of coronary flow during hypoxia (P < 0.05), compared with hearts from the diestrous group. However, despite the effect of proestrus, correlation coefficients between plasma estradiol concentrations and indices of cardiac function were not significant. CONCLUSIONS Our findings indicate that the estrous cycle of the female rat affects cardiac function during hypoxia. This model may be useful to study the impact of the estrous cycle on metabolic and cardiovascular function.